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Endo—Thyroid Dysfunction Thyroid Physiology The thyroid gland is a shield shaped structure that is bilobar. Located in the neck. Composed of a large number of thyroglobulin containing follicular cells. Follicular cells are fat-like cells that are the functional cell of the thyroid. The function of the thyroid gland is to produce and store thyroid hormone. Iodide is the external source needed to produce thyroid hormone. The iodide is pumped from the blood into the follicular cells. It is oxidized by peroxidase and facilitates the combination of a tyrosine molecule from the thyroglobulin and forms either mono or di-iodotyrosine. When two of the di-iodotyrosine combines, we get T4. When a mono-iodotyrosine combines with a di-iodotyrosine, we get T3. The thyroid is involved in the classic negative feedback axis. The hypothalamus releases TRH to the AP. The AP then releases TSH, which will stimulate the thyroid to release T3 and T4. The major thyroid hormone in circulation is T4. T4 is then converted into T3 in the periphery. Thyroid hormone functions to increase metabolism of thyroid hormone. Also necessary for growth and development and maturation of intelligence in children. All major organs are affected by altered levels of thyroid hormone Hypothyroidism Hypothyroidism can be congenital or acquired. Congenital is a preventable cause of mental retardation and impaired growth. All newborns are screened for thyroid deficiency. Can be secondary to lack of thyroid gland Primary Hypothyroidism Chronic autoimmune thyroiditis is also known as Hashimoto’s thyroiditis. It is the most common cause of hypothyroidism. It is characterized by cell and antibody mediated destruction of thyroid tissue. There are high serum autoantibodies to thyroglobin. Affects older females mostly. Usually found with a concurrent autoimmune disease. Iatrogenic can also occur. Thyroidectomy can cause hypothyroidism 2-4 weeks later. Iodine treatment can cause it month to years after. Radiation is dose related. Iodine deficiency is the most common cause of hypothyroidism worldwide but is very rare in the US. Drug induced hypothyroidism is usually associated with a decrease in the production of T3 and T4. Include PTU, methimazole, lithium, amiodarone, or extremely high doses of iodide. Postpartum thyroiditis is seen in pregnancy. Usually resolves after 6-12 months. Preceded by a period of hyperthyroidism. Signs and Symptoms 1) Vary in relation to the magnitude and acuteness of hormone deficiency 2) Slowing of metabolic processes 3) Patients may complain of fatigue, constipation, cold intolerance, SOB, decreased taste, weakness, slow movement and speech, weight gain, hair loss, and decreased sweating Physical Exam 1) Decreased DTR’s 2) Macroglossia 3) Bradycardia 4) Cool/pale skin 5) Loss of lateral 1/3 of eyebrows 6) Puffiness of face/eyelids 7) Poor skin turgor 8) Coarse hair 9) Non-pitting edema 10) Hoarseness 11) Hair loss 12) Thin/brittle nails 13) Goiter Diagnosis 1) Low to normal T4 level 2) Elevation of TSH – most sensitive test 3) Other lab abnormalities include hypercholesterolemia and anemia Treatment 1) Hypothyroidism is usually a permanent condition 2) Goal of treatment is to replace thyroid hormone 3) Oral administration of synthetic thyroxine (T4). Levothyroxine (Synthroid) should be a titrated dose every 4-6 weeks until TSH normalizes Myxedema Coma Myxedema coma is severe hypothyroidism. Presents with decreased mental status, hypothermia, and CV collapse. Can be from long standing hypothyroidism or can be triggered by infection, MI, narcotics, and extreme cold. Usually seen in elderly females. Lab tests will should hypotension, bradycardia, hyponatremia, hypoglycemia, hypoventilation, or hypothermia. It is a medical emergency. Exclude other causes of coma. Draw blood to look for TSH and T4 levels. Treat on clinical suspicion alone. Give glucose, warm them, and treat underlying disease Hyperthyroidism Hyperthyroidism results from the excessive delivery of thyroid hormone to the periphery. Many different causes (see below) Causes Grave’s disease is the most common cause of hyperthyroidism. It is an autoimmune disease. Usually seen in females aged 20-40. There is TSH receptor antibodies which stimulate thyroid growth and thyroid gland secretion during stressful times. Presents with hyperthyroidism, goiter, and exophthalmos. A radioiodine scan will show increased uptake. Toxic multinodular goiter is diffuse hyperplasia of the follicular cells of the thyroid gland. T3 and T4 is produced independent of TSH stimulation. Also should increased uptake on radioiodine scan. Subacute thyroiditis is inflammation of thyroid disease with transient hyperthyroidism due to release of preformed hormone. Common after pregnancy Other rare causes include high levels of iodine intake, TSH secreting pituitary tumor, or ovarian dermoid tumors containing thyroid tissue. Signs and Symptoms 1) Anxiety 2) Weakness 3) Increased appetite 4) Tremor 5) Hyperdefecation 6) ED 7) Thinning hair Physical 1) 2) 3) 4) 5) 6) Hyperactivity Warm/moist skin Exophthalmos Lid lag Softening of nails Rapid speech 8) Emotional liability 9) Increased perspiration 10) Weight loss 11) Palpitations 12) Heat intolerance 13) Muscle weakness 14) Oligomenorrhea 7) Tachycardia 8) Stare 9) Hyperreflexia 10) Pretibial Myxedema 11) Atrial fibrillation Diagnosis 1) Decreased TSH 2) Increased T3 and T4 3) Radioactive iodine uptake will show increased iodine uptake at the thyroid gland Treatment Thionamides inhibit thyroid hormone synthesis by the gland. Includes prophylthiouracil (PTU) and methimazole. Attains a euthyroid state in 3-8 weeks. Beta-blockers ameliorate symptoms such as palpitations, anxiety, and tremors. Propanolol is the agent of choice. Radioiodine ablation is the treatment of choice in the US. Sodium 131 I PO is ingested and it is rapidly concentration in thyroid tissue. Leads to extensive tissue damage and ablation of the thyroid in 6-18 weeks. Thyroidectomy is unpopular in the US. Used for very large or obstructive goiter. Thyroid Storm Thyroid storm is a severe life-threatening hyperthyroidism. Also referred to as thyrotoxicosis. Presents with exaggerate symptoms of hyperthyroidism such as tachycardia, hyperpyrexia, agitation, CHF, delirium, psychosis, stupor, and coma. Can be seen in patients with longstanding hyperthyroidism but is usually triggered by an acute event. It is a medical emergency. Best treated with a beta-blocker and high dose methimazole. Thyroid Cancer Thyroid cancer is a relatively uncommon diagnosis. Has a favorable prognosis. 1% of all cancer diagnosis. Females are affected more often than men. Radiation exposure increases risk of development. Types Papillary is the most common. It grows slowly and has the best prognosis. Follicular is the second most common. It is slightly more aggressive than papillary. Medullary has a poorer prognosis than papillary and follicular. Associated with MEN 2A and 2B. Anaplastic is rapidly growing and has a poor prognosis. Signs and Symptoms 1) Painless, palpable solitary thyroid nodule. Usually discovered by patient or healthcare provider on routine palpation of the neck. 2) Hard, fixed nodules are more suspicious for malignancy. 3) May have anterior cervical LAD. 4) Multiple nodules are usually benign. Single nodules are more suspicious for malignancy. Diagnosis 1) Thyroid function tests are usually normal 2) Fine needle aspiration biopsy (FNAB) – best way to assess for malignancy. Performed with a 25 gauge needle. 3) Radioactive iodine scans – less useful since the advent of FNAB. Cold spots do not take up the iodine, representing malignancy. Hot spots take up the iodine and are usually not malignant Treatment 1) Surgical removal is the treatment of choice 2) Radioiodine ablation to destroy any remaining thyroid cells 3) Treatment with Synthroid post-op to prevent the anterior from secreting TSH.